Responses of neurones in different regions of the rat and cat brain to micro-electrophoretically applied histamine and some related substances including antagonists are reported. Histamine excites most neurones in the hypothalamus but depresses the vast majority of neurones in other structures. Depressant actions of histamine and some inhibitions in the cortex and hippocampus of the rat are antagonized by metiamide, an H2-receptor antagonist. The results lend strong support to the idea of histaminergic transmission in the mammalian brain.